PERIPHERAL T-LYMPHOCYTES FROM WOMEN WITH BREAST-CANCER EXHIBIT ABNORMAL PROTEIN EXPRESSION OF SEVERAL SIGNALING MOLECULES

We examined signaling molecules of peripheral blood T lymphocytes obta ined from women with breast cancer. In 6 of 14 patients, T lymphocytes displayed an impaired ability to translocate NF (e) over cap B p65 (R el-A) following activation by anti-CD3 and IL-2. This observation was made despite normal cytoplasmic levels of the Rel-A protein. We also d etected abnormally low levels of the signaling molecules T-cell recept or (TCR)-zeta, ZAP-70 and p56(lck) in 4 of 14 breast cancer patients, i.e., defects in T-cell signaling molecules. T lymphocytes from 6 of t he 14 patients also exhibited an increased expression of the dual spec ificity phosphatase, map kinase phosphatase-1 (MKP-1). MKP-1 inactivat es MAP kinase and therefore may interfere with the activation of c-jun and c-fos. Abnormalities of I or more signaling molecules were found in 9 of 14 patients; however, only 3 patients had T cells that exhibit ed all 5 defects. Our data have implications for the detection of pote ntially dysfunctional T cells in patients with cancer. For example, th e analysis of only I signaling molecule may allow patients with signif icant defects in T-cell signaling to go unnoticed. Finally; despite im paired Rel-A translocation, T cells were capable of transcribing IL-2. Impairments in the translocation of Rel-B and c-Rel further suggest t hat the NF kappa B family members Rel-A, Rel-B and c-Rel are not requi red for the transcription of IL-2 in the peripheral T lymphocytes of p atients with breast cancer. Int. J. Cancer 78:16-20, 1998. (C) 1998 Wi ley-Liss, Inc.